RESUMO
BACKGROUND: Pancreatic cancer is common in elderly persons, and less than 20% of patients present with localized, potentially curable tumors. METHODS: We compared the methylated sites and genes in pericarcinous tissues compared to cancer tissue, and blood compared to pericarcinous tissues in order to harvest methylation markers for putative diagnostic and therapy monitoring purposes. RESULTS: Of 15,397 CpG sites detected in 7,440 genes, 5,605 (36.4%, 5,605 of 15,397) CpG sites were hypomethylated and 5,870 (38.12%, 5,870 of 15,397) CpG sites were hypermethylated. We then performed Gene Ontology (GO) and KEGG analysis to systematically characterize the ten significantly differentially methylated genes: PTPRN2, MAD1L1, TNXB, PRDM16, GNAS, KCNQ1, TSNARE1, HDAC4, TBCD, and DIP2C. Meanwhile, function analysis of genes with differentially methylated sites located in promoter regions of overlap group was also performed. According to previous studies, we further screened 22 pancreatic cancer related key genes. The results suggested that these key genes can influence methylation. GO and KEGG analysis indicated that these genes are involved in a wide range of functions. CONCLUSIONS: The identification of differentially methylated genes in this study provides valuable information for liquid biopsy methylation markers in pancreatic cancer.
RESUMO
Cutaneous T-cell lymphoma (CTCL) represents a rare group of extranodal T-cell lymphoproliferative diseases. Due to poor clinical outcome of CTCL, there is an urgent need for new and improved therapies. A small molecule, IPA-3, which inhibits p21-activated kinase 1 (PAK1), has shown therapeutic potential in various types of malignancies. In the present study, the anti-tumor effect of IPA-3 and its underlying molecular mechanism was evaluated. High expression of phosphorylated-PAK1 (pho-PAK1) was seen in CTCL lesional skin compared to benign inflammatory dermatoses. IPA-3 could significantly inhibit the proliferation of 3 CTCL lines in a dose- and time-dependent manner. The percentage of apoptotic cells was higher in the treatment group. Further, IPA-3 treatment caused increased EGR1 protein levels and decreased apoptosis-related BCL-2 and pho-BAD protein levels. In summary, inhibition of pho-PAK1 has significant anti-tumor effects in CTCL cells and it can be explored as a future therapeutic option.
